Background: Areca nut (Areca Catechu) is considered to be the fourth extremely prevalent addictive psychoactive substance consumed widely by about 10%–20% of the world population. Due to its theological and cultural acceptance, areca nut is chewed in different forms and formulations. It has been observed that people who chew supari (areca nut) exclusively for many years suffer from diabetes mellitus, coronary artery disease (CAD), oral submucous fibrosis, and oral cancer. We, therefore, planned to see its association with various cardiovascular ailments at our center. Materials and Methods: This was a single-center observational study carried out on people chewing areca nut exclusively (no other toxic or addicting substance) attending cardiac outpatient department (OPD) in National Heart Institute and Research Centre, Delhi, India. The subjects data were collected regarding the history of the disease, consumption of areca nut, and socioeconomic status with relevant work up. Results: There were 17 subjects who primarily chewed areca nut; 11 of them had CAD, diabetes, oral submucous fibrosis, and aplastic anemia. Further, one particular case not only suffered oral cancer but also had two episodes of myocardial infarction, but continued to chew areca nut. The second episode of myocardial infarction was fatal. Conclusion: Areca nut chewing is also associated with significant cardiovascular morbidities besides oral cancer. In such preparations, the risk of some other toxic substances together with areca nut cannot be eliminated as no empirical analysis has been carried out to the best of our knowledge and belief. In order to clarify its effect on other vascular diseases, further work with a larger sample size is required.

Areca nut is the seed part of Areca catechu that grows in the tropical Pacific, Asia, and parts of eastern Africa. Areca nut is one of the world’s most abused drugs.[1] Areca nut is often chewed alone or cut into fine pieces rolled in betel leaves (paan) or paan and tobacco, both usually referred to as betel quid. Areca nut is chewed in a number of fragrant preparations by itself. In diverse populations and regions, the composition of areca nut varies.[2] After alcohol, caffeine, and nicotine, it is the fourth most common human self-ordered psychoactive substance.[3] One might defensibly call it a social evil, because its social acceptability in the Indian subcontinent is too high, particularly in different religions. Unlike other psychoactive substances such as tobacco and alcohol, it has strong cultural acceptability across all demographic groups in the subcontinent. Areca nut’s active ingredient is arecoline that is known to cause addiction; however, there is no direct evidence for it.[4] Areca nut is known to cause damage to the oral mucosa, oral pharynx, dental tissue, and gastrointestinal tract, but it is likely after the cardiovascular system, genitourinary system, hematopoietic system, and other organs.[5] Unlike tobacco and alcohol, areca nut is not considered a public health issue. We recently found many cases of the oral lesion in combination with cardiovascular disease in which areca nut played a significant role in their etiopathogenesis.[6]

In the traditional plate, the inclusion of the areca nut is considered a must, as areca nuts are thought to increase wealth. The nut is given as a mark of respect to visitors, along with a betel leaf. Areca quid chewing (areca root, areca nut, and lime) is a tradition in India that is 2000 years old. Tobacco was known about the seventeenth century.[7],[8] The pervasiveness of areca nut consumption with or without tobacco in India is very strong and is, therefore, socially acceptable and culturally acceptable. It is consumed in rural areas by about 34.7% of males as compared with 32.4% of females. For urban areas, male consumption is about 37.8% and female consumption is about 29.7%. Areca nut products are commonly used by young people, where 16.4% use it on a regular basis and 13% sporadically use it. Even the well-educated part of society is overwhelmingly using areca nut, where 12.5% do it daily and 27.5% do it rarely.[9],[10] Because of its addictive nature, Sikhs and Buddhists are prohibited from using areca nut. Due to its socio-cultural acceptability, Hindus chewed it not only alone but also often with betel leaf (piper Areca).[11] Muslims and Jains do not generally chew areca nut alone. Interestingly, in most of the famous paan masalas and Gutkha consumed by Hindus and Muslims alike, areca nut has become an essential ingredient over the past 50 years.[4],[11] This prompted us to evaluate all aspects of areca nut in order to raise the awareness of medical fraternity and public health officials as well as people at large who become their victims taking into account the damage they inflict on an individual and society.

Materials and methods

We carried out an evidence-based analysis study in people attending the cardiac outpatient department (OPD) of National Heart Institute, New Delhi, India, who chewed preparations that contain only areca nut and no other addictive substances such as tobacco and alcohol. Data on the history of the disease, consumption of areca nut and socioeconomic status, and important laboratory work were collected from the subject. The data were collected during the period 2015–2017 in the cardiac OPD of the National Heart Institute and Research Centre. The subjects age included in the study range was between 20 and 74 years (mean age 57 years). Both sexes were included in the study. Socioeconomic status was categorized as I–IV: I (very wealthy financially); II (wealthy financially); III (middle class); and IV (poor). The ethnicity of subjects was also noticed in our study. The history of consumption of areca nut preparation by subjects was asked in the regular OPD by our cardiologist, and important laboratory work was collected from the patients. Some subjects evidence was also taken after the consent of subjects in our cardiac OPD; some pictorial evidence has been mentioned in [Figure 1] and [Table 1].

It was found that of 17 individuals who were taking only areca nut, 11 suffered from coronary artery disease (CAD), diabetes, submucosal fibrosis, oral cancer, aplastic anemia, and xanthomas [Table 1]. There was a higher prevalence of cardiovascular diseases among subjects who exclusively chew areca nut, with hypertension (54.54%), CAD (27.27%), oral cancer (18.18%), and aplastic anemia (18.18%). The sexual pervasiveness of areca nut consumption in all subjects was found to be 52.94% in males and 47.05% in females. The impact and acceptability of areca nut in various socioeconomic strata (SES) categories was as follows: SES I = 9.09%; SES II = 27.27%; SES III = 45.45%; and SES IV = 18.18%.

Discussion

As consumption of areca nut alone is not mentioned by subjects and usually not asked by physicians in routine history taking, its clinicopathological effect on the human system goes mostly unreported by internists and cardiologists. Most of its adverse effects have been noted by dental surgeons and/or oral cancer surgeons. However, we do come across some cardiovascular subjects who give a history of chewing areca nut alone when confronted with evidence of bad oro-dental health. It is only then they accept to be chewing areca nut. Unlike smoking habit, taking areca nut is more common among South Asian men and women. This habit is passed down to the next generation. Its ill effects are related to cholinergic action of its alkaloid constituent— arecoline. Its use can diminish the effects of antimuscarinic drugs and potentiate the action of other cholinergic agonists, and in the final case a cholinergic toxicity syndrome can result. Soon after chewing areca nut, they demonstrate the inhibitory action of arecoline on GABA because of the antagonism of the anxiolytic effect of benzodiazepine and antidepressant.[12] Other interactions have been found with: amantadine, phenothiazine, olanzapine, molindone, loxapine, and haloperidol.[13] They result in an increase of the extrapyramidal effects. The use of areca nut can slow and raise heart rate, so it is possible that it may interact with beta-blockers, calcium antagonists, and digoxin. Because arecoline can have an effect on sugar levels, caution is advised when using other medications that vary glucose level in blood.[14] The arecoline cytotoxicity and carcinogenic properties are potentiated by the modern use of alcohol and smoking. This is a very pertinent point because many subjects in India, particularly males, are addicted to smoking as well as alcohol, thus suffering from acute myocardial infarction at a young age because of their addiction to areca-nut-containing pan masala, smoking, and alcohol all three. The use of arecoline together with caffeine, guarana, and ephedra (stimulant herbs) increases the choline excitatory activity of areca nut.[13]

This study indicates chewing of areca nut leads to the risk of CAD besides its potential to cause cancer in oral cavity, pharynx, and throat in subjects who chewed areca nut alone or mixed with other deleterious substances. This is corroborated by a Taiwanese study that has reported a linkage between areca nut chewing and cardiovascular diseases in women.[14] Although many other studies have reported that elderly people who chewed areca nut had a higher risk of all-cause mortality (hazard ratio = 1.19, 95% confidence interval [CI]: 1.05, 1.35), and cerebrovascular diseases death (hazard ratio = 1.66, 95% CI: 1.19, 2.30), compared with who did not consume areca nut.[15] There are some other studies that support the outcomes of our study. It has also been reported that areca nut causes hypertension, arrhythmia, and CAD.[15] It is also mentioned that homocysteine level increases among chronic users of areca nut.[16] Further several incidences of extra systoles have been reported in habitual users of areca nut. Tachycardia begins within 2min of its consumption and lasts at least 20min. This is another evidence of the cardiovascular effects of areca nut.[17] They are associated with a higher risk of ischemic cardiopathies.[18] Arecoline can cause vasospasms in coronaries. This is probably due to endothelial damage following arecoline parasympathomimetic action.[13] Damage to endothelial cells can be considered as one of the causes of CAD. Chronic use of areca nut can cause a decrease in B12 levels in the blood, but also thiamine and vitamin D are reported to be depleted by this habit. It is not clear if vitamin depletion is due to arecoline or other substances contained in the betel nut preparations.[19]

Conclusion

The study shows that chewing of areca nut in any form appears to be a risk factor for CAD, hypertension, and diabetes mellitus, in addition to cancer. Presence of addictive toxic materials in various preparations cannot be ruled out. It is, therefore, recommended that systematic chemical analysis of various preparations of areca nut available in the market followed by clinical studies on their cardiotoxic effects, including systematic large-scale studies to elucidate its role in different vascular diseases, be carried out.